Enhanced engraftment of stem cells. There is an urgent need for methods to improve the engraftment efficiency of autologous and allogeneic hematopoietic stem cells (HSC) after myeloablative therapy. Although mobilized peripheral blood and umbilical cord blood (CB) have expanded the availability of donor cells, a significant cause of morbidity and mortality is the failure to obtain complete and rapid hematopoietic reconstitution. This is most often due to the injection of low numbers of CD34+ cells; insufficient homing, retention and differentiation of donor cells; and/or lack of facilitator cell help (T cell help in engraftment and/or other cell populations). To address these problems, we have developed a proprietary approach to cell targeting using bispecific antibodies (BiMab). A pair of antibodies is chemically heteroconjugated to target cells to specific antigens found at sites of injury. Our preliminary data have shown that three different BiMabs enhance the retention of targeted cells in vivo. In Phase I we will prepare an expanded set of BiMabs to demonstrate their ability to improve hematopoietic cell recovery and engraftment of irradiated mice. The BiMab that shows the greatest capacity to enhance engraftment will be selected for further development of a clinical candidate in Phase II. Enhanced engraftment of stem cells Hematopoietic stem cell (HSC) transplantation is a common therapeutic option developed to treat hematologic malignancies and certain genetic and immunological disorders. Efficient delivery, retention and differentiation of HSC remain major limitations to the success of bone marrow engraftment. Bispecific antibodies (BiMab) recognizing a bone marrow-specific target and an antigen on hematopoietic stem cells provide a novel means to greatly improve the efficiency of autologous and allogeneic stem cell therapy for a broad spectrum of diseases. ? ? ?
